The phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinases involved in the regulation of a network of signal transduction pathways that control a range of cellular processes. PI3Ks are classified into four distinct subfamilies, named class I, II, III and IV, based upon their substrate specificities. Of these, class IA PI3Ks possess a p110α, p110β, or p110δ catalytic subunit complexed with one of three regulatory subunits, p85α, p85β or p55δ. A single class IB PI3K exists, comprising a p110γ catalytic and a p101 regulatory subunit. Class IA PI3Ks are activated by receptor tyrosine kinases, antigen receptors, G-protein coupled receptors (GPCRs), and cytokine receptors, and the class IB PI3K is activated by GPCRs. The class IA PI3Ks primarily generate phosphatidylinositol-3,4,5-triphosphate (PI(3,4,5)P3), a second messenger that activates the downstream target AKT. The consequences of biological activation of AKT include tumour progression, proliferation, survival and growth, and there is significant evidence suggesting that the PI3K/AKT pathway is dysregulated in many human cancers. Additionally, PI3K activity has been implicated in endocrinology, cardiovascular disease, immune disorders and inflammation. As such, compounds which are able to modulate PI3K have important therapeutic potential.
WO08/064018 discloses compounds for inhibiting the activity of PI3K-delta.